CA2956464C - Inhibiteurs a base de bisamidinium pour le traitement de la dystrophie myotonique - Google Patents

Inhibiteurs a base de bisamidinium pour le traitement de la dystrophie myotonique Download PDF

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Publication number
CA2956464C
CA2956464C CA2956464A CA2956464A CA2956464C CA 2956464 C CA2956464 C CA 2956464C CA 2956464 A CA2956464 A CA 2956464A CA 2956464 A CA2956464 A CA 2956464A CA 2956464 C CA2956464 C CA 2956464C
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compound
formula
compounds
cch
alkyl
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CA2956464A
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English (en)
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CA2956464A1 (fr
Inventor
Steven C. Zimmerman
Long M. LUU
Lein T.T. NGUYEN
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University of Illinois System
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University of Illinois System
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des composés de formule (I), des compositions et des méthodes thérapeutiques. Les composés et les compositions peuvent être utilisés par le traitement de l'atrophie myotonique. Les composés peuvent sélectivement être liés aux répétitions de CUG dans l'ARN ou de CTG dans l'ADN et inhibe la réplication des acides nucléiques. Des agents thérapeutiques ciblant l'ARN pour le traitement de l'atrophie myotonique de type 1 (DM1) sont décrits. Selon un mode de réalisation, deux liants de bisamidinium sont liés au moyen de la chimie click pour former un hétérodimère qui est un inhibiteur puissant du complexe MBNLl-rCUGexp (Ki = 25 ± 8 nM) et relativement non toxique pour les cellules HeLa, dissout les foyers nucléaires, corrige >80 % de l'épissage alternatif à infrarouge mal régulé dans les cellules du modèle DML (1 µM) et montre une amélioration des phénotypes de maladies dans le modèle de la drosophile DML
CA2956464A 2014-08-08 2015-08-10 Inhibiteurs a base de bisamidinium pour le traitement de la dystrophie myotonique Active CA2956464C (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462034932P 2014-08-08 2014-08-08
US62/034,932 2014-08-08
PCT/US2015/044526 WO2016023039A1 (fr) 2014-08-08 2015-08-10 Inhibiteurs à base de bisamidinium pour le traitement de la dystrophie myotonique

Publications (2)

Publication Number Publication Date
CA2956464A1 CA2956464A1 (fr) 2016-02-11
CA2956464C true CA2956464C (fr) 2023-05-09

Family

ID=55264707

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2956464A Active CA2956464C (fr) 2014-08-08 2015-08-10 Inhibiteurs a base de bisamidinium pour le traitement de la dystrophie myotonique

Country Status (3)

Country Link
US (2) US9376421B2 (fr)
CA (1) CA2956464C (fr)
WO (1) WO2016023039A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3145430B1 (fr) 2014-05-18 2019-07-03 Eximo Medical Ltd. Système pour l'ablation de tissus au moyen de laser pulsé
US11242326B2 (en) 2017-08-25 2022-02-08 The Board Of Trustees Of The University Of Illinois Multivalent ligand for myotonic dystrophy

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2698865B2 (ja) 1994-08-08 1998-01-19 仲昭 大澤 筋緊張性ジストロフィー症治療剤
US20050037954A1 (en) 2001-03-23 2005-02-17 Masaki Hirashima Novel agents for ameliorating motor disorder
US6987123B2 (en) 2001-07-26 2006-01-17 Cadila Healthcare Limited Heterocyclic compounds, their preparation, pharmaceutical compositions containing them and their use in medicine
GB0613518D0 (en) 2006-07-06 2006-08-16 Phytopharm Plc Chemical compounds
EP2591795B1 (fr) 2007-02-23 2018-02-28 The Research Foundation Of State University Of New York Composés de ciblage d'arn, et procédés de fabrication et d'utilisation de ceux-ci
WO2009105691A2 (fr) 2008-02-21 2009-08-27 State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The University Of Oregon Utilisations de pentamidine et de composés associés
US8754084B2 (en) 2012-03-27 2014-06-17 The Board Of Trustees Of The University Of Illinois Therapeutic methods and agents for treating myotonic dystrophy

Also Published As

Publication number Publication date
US20180215736A1 (en) 2018-08-02
US9376421B2 (en) 2016-06-28
US20160052914A1 (en) 2016-02-25
CA2956464A1 (fr) 2016-02-11
WO2016023039A1 (fr) 2016-02-11
US10266520B2 (en) 2019-04-23

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